Indomethacin potentiates endotoxin‐induced blood flow reduction and histological injury in rat gastric mucosa

Piqué, Josep M.; Yasuda, Yoshikazu; Whittle, Brendan J.R.; Leung, Felix W.; Guth, Paul H.

doi:10.1111/j.1476-5381.1988.tb11481.x

Cited by 14 publications

(3 citation statements)

References 18 publications

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“…The beneficial effects of indomethacin are correlated with decreased levels of nitrite and prostaglandins in biological fluids from endotoxemic rats (Futaki et al , 1997). Indomethacin has also shown to abolish or significantly attenuate the decrease in blood pressure (Fatehi-Hassanabad et al , 1996) or have no significant effect on blood pressure in endotoxemic rats (Pique et al , 1988; Vayssettes-Courchay et al , 2002). Vasoconstriction and increased blood pressure after systemic inhibition of NOS results not only from withdrawal of vasodilator NO, but from increased activity of the vasoconstrictor systems, including sympathetic nervous and renin-angiotensin systems, and production of endothelins and 20-hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite derived via cytochrome P450 (CYP) (Fleming, 2001; Roman, 2002; Zatz and Baylis, 1998).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

et al. 2008

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Increased production of nitric oxide (NO) and prostaglandins contribute to development of hypotension during endotoxemia. We have previously demonstrated that endotoxemia-induced increase in NO production suppresses renal cytochrome P450 (CYP) 4A expression and activity, and that selective inhibition of inducible NO synthase (iNOS) with 1,3-PBIT restores renal CYP 4A protein and activity and mean arterial pressure (MAP). By using cyclooxygenase (COX) inhibitor indomethacin, we investigated herein whether prostaglandins, via NO production, inhibit renal CYP 4A1 protein expression and CYP 4A activity and contribute to the endotoxin-induced hypotension. In conscious male Sprague-Dawley rats, endotoxin (10 mg/kg, intraperitoneal (i.p.)) reduced MAP, increased serum nitrite and bicyclo PGE 2 levels, renal nitrite production and iNOS protein expression, and decreased renal CYP 4A1 protein expression and CYP 4A activity after 4 h injection. All of the endotoxin-induced changes, except for increase in renal nitrite production, were prevented by indomethacin (5 mg/kg, i.p. 1 h after endotoxin). The effects of indomethacin on the endotoxininduced decrease in MAP, CYP 4A1 protein expression and CYP 4A activity were minimized by the CYP 4A inhibitor, aminobenzotriazole (50 mg/kg, i.p. 1 h after endotoxin). These data suggest that prostaglandins produced during endotoxemia increase iNOS protein expression and NO synthesis, and decrease CYP 4A protein expression and CYP 4A activity and that inhibition of iNOS or COX restores renal CYP 4A protein level and CYP 4A activity and MAP presumably due to increased production of arachidonic acid metabolites derived from CYP 4A.

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Section: Introductionmentioning

confidence: 99%

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

et al. 2008

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“…In this context, various events relating to the inflammatory reaction have been analyzed, such as the expression of adhesion molecules, the infiltration of leukocytes, and cytokine-mediated apoptosis. Pique et al [1988] studied the effects of indomethacin on endotoxin-mediated suppression of gastric mucosal blood flow and the subsequent gastric damage in anesthetized rats, and suggested that endogenous prostaglandin plays a protective role in endotoxininduced gastric mucosal microcirculatory disturbances and mucosal damage. Harada et al [1999] studied stressinduced gastric mucosal injury in rats, and showed that treatment with indomethacin before the stress inhibited the increase in 6-keto-PGF1α levels and markedly reduced mucosal blood flow.…”

Section: Discussionmentioning

confidence: 99%

Septic shock induced by microbial products and indomethacin

Moriya

Ohno

Miura

et al. 2002

Drug Development Research

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Lethal toxicity was induced in mice by sequential administration of β-glucan and indomethacin. Whole cell preparations of Gram-positive bacteria, Gram-negative bacteria, and fungi also showed a similar toxicity. However, bacterial lipopolysaccharides (LPS) alone were not toxic. After the indomethacin administration, the sensitivity of mice to LPS was significantly elevated and the animals died following only a 0.1-µg intravenous administration. An accumulation of leukocytes in the liver and enhancement of TNF, IL-6, and MIP-2 concentrations were noted. Antibiotic treatment prolonged the survival of mice. The toxicity resembles septic shock, and is strongly related to microbial translocation and endotoxin absorption from the gut. Drug Dev. Abbreviations used: BRM = biological response modifier; CA = Candida albicans; CAWS = Candida water soluble polysaccharide fraction; COX = cyclooxygenase; CSBG = Candida solubilized cell wall β-glucan; CSF = colony stimulating factor; DB = degree of branching; DMSO = dimethylsulfoxide; IFN = interferon; IL-6 = interleukin-6; LPS = lipopolysaccharide; MW = molecular weight; NaClO = sodium hypochlorite; NK= natural killer; NSAIDs = nonsteroidal anti-inflammatory drugs; OX-CA = NaClO oxidized Candida albicans; PG= prostaglandin; SPG = sonifillan (schizophyllan); SSG = soluble β-glucan of Sclerotinia sclerotiorum IFO9395; YPG = culture medium containing yeast ext., polypeptone, and glucose; Z-CA= zymolyase solubilized CA; ZYC= zymocel; ZYM = zymosan A.

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“…In experimental studies, systemic administration to rats of doses of bacterial endotoxin in the range of mg/kg has been reported to induce profound changes in gastrointestinal function such as diarrhoea, reduction in gastric mucosal blood flow and gastrointestinal mucosal damage [3,4]. These changes last for several hours after challenge and are related with activation of the immune response and transcriptional synthesis of proteins.…”

Section: Introductionmentioning

confidence: 99%

Nitrergic Modulation of Gastrointestinal Function During Early Endotoxemia

Quintana

Barrachina²,

Esplugues³

2006

CPD

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After bacterial infection, the host reacts by signalling to the central nervous system where a cascade of physiologic, neuroendocrine and behavioural processes is orchestrated, collectively termed the acute phase response. Endotoxemia following Gram-negative bacterial infection induces a wide array of effects, including fever, loss of appetite and changes in gastrointestinal function that attempt to eliminate the challenge and restore homeostasis. Systemic administration of low doses of endotoxin (5-40 microg/kg) to rats is associated with changes in gastrointestinal motor function, inhibition of gastric acid secretion and increase in the gastric mucosal resistance to damage. These changes are rapid in onset (observed within one hour), not related to vascular dysfunction, and appear to be mediated by mechanisms that involve the peripheral and the central nervous system. Nitric oxide (NO) plays a central role in the physiology of the gastrointestinal tract and its response to illness. Accumulated evidence supports an increase of NO synthesis in the brainstem, as well as in the gastric myenteric plexus thirty minutes after endotoxin administration. Such a synthesis is due to constitutive nitric oxide synthase (NOS) and occurs before the induction of NOS takes place. In this review we provide experimental evidence supporting the hypothesis that activation of a physiologic mechanism, mediated by the autonomic and the central nervous systems as well as constitutive NOS isoforms, is involved in acute changes of gastrointestinal function during early endotoxemia.

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Indomethacin potentiates endotoxin‐induced blood flow reduction and histological injury in rat gastric mucosa

Cited by 14 publications

References 18 publications

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

Prostaglandins inhibit cytochrome P450 4A activity and contribute to endotoxin-induced hypotension in rats via nitric oxide production

Septic shock induced by microbial products and indomethacin

Nitrergic Modulation of Gastrointestinal Function During Early Endotoxemia

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